Pain management is essential because even when the underlying disease process is stable, uncontrolled pain prevents patients from working productively, enjoying recreation, or taking pleasure in their usual roles in the family and society. Chronic pain may have a myriad of causes and perpetuating factors, and therefore can be much more difficult to manage than acute pain, requiring a multidisciplinary approach and customized treatment protocols to meet the specific needs of each patient.

Optimal treatment may involve the use of medications that possess pain-relieving properties, including some antidepressants, anticonvulsants, antiarrhythmics, anesthetics, antiviral agents, and NMDA (N-methyl-D-aspartate) antagonists. NMDA-receptor antagonists, such as dextromethorphan and ketamine, can block pain transmission in dorsal horn spinal neurons, reduce nociception, and decrease tolerance to and the need for opioid analgesics. [Anesth Analg 2001 Mar;92(3):739-44] By combining various agents which utilize different mechanisms to alter the sensation of pain, physicians have found that smaller concentrations of each medication can be used.

Topical and transdermal creams and gels can be formulated to provide high local concentrations at the site of application (e.g., NSAIDs for joint pain), for trigger point application (e.g., combinations of medications for neuropathic pain), or in a base that will allow systemic absorption. Side effects associated with oral administration can often be avoided when medications are used topically. Studies suggest that there are no great restrictions on the type of drug that can be incorporated into a properly compounded transdermal gel. When medications are administered transdermally, they are not absorbed through the gastrointestinal system and do not undergo first-pass hepatic metabolism.

We work together with patient and practitioner to solve problems by customizing medications that meet the specific needs of each individual. Please contact our compounding pharmacist to discuss the dosage form, strength, and medication or combination that is most appropriate for your patient.

Neuropathic Pain

Treatment for Neuropathic PainNeuropathic pain is caused by an injury to the nervous system; examples include phantom limb, spinal cord injury pain, post-herpetic neuralgia, sciatica, trigeminal neuralgia, and drug-induced neuropathy. Painful neuropathy is a common and often progressive complication of diabetes. Patients frequently report symptoms of tingling, burning, lancinating pain, or exaggerated pain responses. The natural history of the disease may vary from intermittent mild symptoms to severe chronic daily pain; the latter is often associated with diminished quality of life. Severe chronic neuropathic pain is a challenge to treat, and often oral medications cannot be administered in adequate doses due to potential side effects. As a result, many patients remain untreated or undertreated. However, topical pain relievers are an option, and often produce fewer side effects with improved patient compliance.

Kopsky et al. described two cases treated effectively with topical amitriptyline 5% and 10%. The first patient was a 39 y.o. man, suffering from severe intractable neuropathic pain in feet and hands, due to diabetes mellitus type II (DM-II). After application of amitriptyline 5% the patient experienced complete relief only in the hands, whereas after application of amitriptyline 10%, a total reduction of pain occurred within 20 minutes, lasting the whole day. The second patient was a 57 y.o. man, suffering for 10 years from progressive sensory disturbances in both feet and increasing pain due to chronic idiopathic axonal polyneuropathy (CIAP). Amitriptyline 5% cream reduced pain in the toes nearly completely, but not in the heels. Amitriptyline 10% reduced pain in the feet; however, systemic adverse effects occurred, mainly drowsiness. These two cases suggest an analgesic dose-response effect of topical amitriptyline in painful neuropathy.

Ther Adv Endocrinol Metab. 2011 Feb;2(1):27-38.Clinical Approach to the Treatment of Painful Diabetic Neuropathy.Click here to access the PubMed abstract of this article.

Pain Pract. 2011 Jun 16. [Epub ahead of print]High Doses of Topical Amitriptyline in Neuropathic Pain: Two Cases and Literature Review.Click here to access the PubMed abstract of this article.

Lidocaine 5% as a “plaster” is indicated for the symptomatic relief of neuropathic pain associated with previous herpes zoster infection (i.e. postherpetic neuralgia [PHN]) in adults, and is well tolerated.

Drugs. 2009 Oct 22;69(15):2149-65.Lidocaine 5% medicated plaster: a review of its use in postherpetic neuralgia.
Garnock-Jones KP, Keating GM.Click here to access the PubMed abstract of this article.

This study evaluated the effects of a topical gel containing baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) on numbness, tingling, and pain caused by chemotherapy-induced peripheral neuropathy. The study concluded that BAK-PLO was well tolerated without evidence of systemic toxicity and appeared to somewhat improve symptoms of CIPN.

Study subjects with moderate to severe peripheral neuropathic pain found that use of topical 2% amitriptyline/1% ketamine cream was well tolerated and was associated with long-term reduction in perceived pain.

Combinations of synergistic drugs can be customized for the patient with chronic pain, and topical or transdermal formulations offer excellent alternatives, sometimes with fewer side effects compared to the same drugs when taken orally. A multicenter, double-blind, randomized, placebo controlled study was conducted to evaluate the efficacy and safety of amitriptyline 4%/ketamine 2% [NP-H] and amitriptyline 2%/ketamine 1% [NP-L] topical creams versus placebo in 251 PHN patients. NP-H was numerically superior to NP-L cream and placebo, and appears to be the optimal concentration for PHN treatment. Less than 5% of subjects who applied NP-H had detectable serum levels of amitriptyline or ketamine.

The following article discusses the use of topical ketamine 0.5% (5 mg/ml) gel, applied as a thin film two to three times daily over the skin where pain was severe. Topical ketamine reduced pain for patients with postherpetic neuralgia with no systemic side effects.

Neurology 2003;60:1391-1392Topical ketamine treatment of postherpetic neuralgia
No abstract available. Click here to purchase the full article on line.

The following randomized, double-blind, placebo-controlled study assessed the analgesic efficacy of topical administration of 3.3% doxepin hydrochloride, 0.025% capsaicin or a combination applied daily for 4 weeks in 200 adult patients with chronic neuropathic pain, and reported that all three preparations significantly reduced overall pain.

Midrin®
A multicenter, double-blind, randomized, parallel-group study concluded that “several parameters suggest that isometheptene mucate, dichloralphenazone with acetaminophen may have a slight advantage compared with sumatriptan succinate in the early treatment of mild-to-moderate migraine.”Headache. 2001 Apr;41(4):391-8.Comparative study of a combination of isometheptene mucate, dichloralphenazone with acetaminophen and sumatriptan succinate in the treatment of migraine.
Freitag FG et al.

If you or your patient have benefited from treatment with Midrin®, you’ll be happy to know that even though Midrin® is no longer commercially manufactured, we can compound a preparation containing isometheptene, acetaminophen, and dichloralphenazone (or chloral hydrate when dichloralphenazone is unavailable).

The following article concludes: A fixed combination of indomethacin 25 mg, prochlorperazine dimaleate 4 mg, and caffeine 75 mg is significantly more effective than sumatriptan in the acute treatment of migraine attacks versus sumatriptan 25 mg, both rectal suppositories.

Headache. 2003 Sep;43(8):835-44Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine versus sumatriptan in acute treatment of multiple migraine attacks: a multicenter, randomized, crossover trial.Click here to access the PubMed abstract of this article.

The following article concludes: Oral therapy with a combination of LAS (equivalent to 900 mg ASA) and metoclopramide 10 mg was superior to placebo with therapeutic gains of 30% and 31% for the first treated attack, and was comparable to 100 mg sumatriptan.

Funct Neurol. 2000;15 Suppl 3:196-201The effectiveness of combined oral lysine acetylsalicylate and metoclopramide (Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral sumatriptan.Click here to access the PubMed abstract of this article.

NSAID Therapy

To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects.Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.

This study concluded that topical NSAIDs, when used for treatment of pain resulting from strains, sprains or sports or overuse-type injuries, can provide good levels of pain relief without the systemic adverse events associated with oral NSAIDs.

“Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes.”

BMJ. 1995 Jul 1;311(6996):22-6Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.
Free full text article available at bmj.com:http://bmj.bmjjournals.com/cgi/content/full/311/6996/22

This study concludes that topical NSAIDs have not been associated with renal failure.

QJM. 1995 Aug;88(8):551-7Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.Click here to access the PubMed abstract of this article.

The following article concludes: “Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.”

The following article reports “The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure.”

Sever disease is the most common cause of heel pain in pre-pubertal children. This inflammatory condition is a result of minor repetitive trauma and typically occurs during a growth spurt or at the beginning of a new sport season. A case report described the use of topical ketoprofen 10% gel to relieve pain and inflammation.

Phys Ther. 2006 Mar;86(3):424-33Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.Click here to access the PubMed abstract of this article.

Findings of this study demonstrate that “following topical application in a patch, ketoprofen shows rapid and sustained delivery to the underlying tissues without a significant increase of the plasma drug concentration.”

Reduction of spontaneous pain and pain on active movement in the topical ketoprofen spray group was significantly greater than in the oral ketoprofen treatment group, irrespective of sprain severity. Regarding mobility impairment and ankle swelling, topically-applied ketoprofen treatment turned out to be significantly superior to orally administered ketoprofen treatment. Additionally, the topical preparation was well tolerated, whereas ketoprofen tablets caused gastrointestinal side effects in some patients.

Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with higher tissue levels beneath the site of application and a reduced incidence of systemic (such as gastrointestinal) adverse effects.

A double-blind placebo-controlled crossover trial showed that in patients with Complex Regional Pain Syndrome (CRPS; also known as Reflex Sympathetic Dystrophy), topical application of ketamine 10% cream caused a reduction in allodynia, a most unpleasant aspect of this condition. This study shows promise for the use of topical ketamine as opposed to parenteral and oral forms which often result in undesirable side effects.

“Lidocaine lollipop is a promising form of local oropharyngeal anesthesia for EGD. Its use resulted in sparing the use of intravenous sedation. It is well tolerated and safe and may be particularly important in the elderly, patients with comorbidities, and office-based endoscopy. “

The following article concludes: “LAT gel (4% lidocaine, 1:2000 adrenaline, 0.5% tetracaine) worked as well as TAC gel (0.5% tetracaine, 1:2000 adrenaline, 11.8% cocaine) for topical anesthesia in facial and scalp lacerations. Considering the advantages of a noncontrolled substance and less expense, LAT gel appears to be better suited than TAC gel for topical anesthesia in laceration repair in children.”

The following article reported that a triple-anesthetic gel containing benzocaine, lidocaine, and tetracaine (“BLT”) applied prior to treatment with a 532-nm KTP laser resulted in significantly lower pain scores than with 3 other topical anesthetics at 15, 30, 45, and 60 minutes after application.

The discovery of peripheral opioid receptors has become the scientific basis for topical use of opioids in malignant and nonmalignant ulcers and oropharyngeal mucositis. A systematic review assessed the quality of published literature and examined whether topical opioids are effective in controlling pain in palliative care settings. Eighteen studies favored topical opioids in pain relief, but time to onset and duration of analgesia varied widely, perhaps due to variances in formulations. “N-of-1 trials should be encouraged for specific clinical circumstances.”J Pain Symptom Manage. 2009 May;37(5):913-7.Effectiveness of topical administration of opioids in palliative care: a systematic review.Click here to access the PubMed abstract of this article.

B&O Suppositories

B&O Suppositories are used for relief of moderate to severe pain associated with rectal or bladder spasms that may occur postoperatively or secondary to cancer. Periodically, these have been on back order. When medications are not commercially available, call our compounding pharmacy.

At Columbia- New York Presbyterian Hospital, physicians examined whether acetaminophen with codeine administered per rectum is an effective alternative for pain control compared with oral administration after an adenotonsillectomy. Equivalent postoperative pain control was achieved with suppositories and oral medication, with few side effects and good tolerance. Furthermore, many parents preferred the suppositories to oral medication in maintaining postoperative pain control because of ease of administration.

Laryngoscope 2006 Aug;116(8):1485-8Comparison of oral versus rectal administration of acetaminophen with codeine in postoperative pediatric adenotonsillectomy patients.Click here to access the PubMed abstract of this article.

The use of topical morphine gel is reported in two children with epidermolysis bullosa, where acute inflammatory pain is a major symptom and where effective analgesia is a major clinical problem.

Morphine sulfate 10 mg in Intrasite gel was applied topically to skin ulcers of hospice inpatients. The topical morphine was not absorbed in the majority of patients, suggesting any analgesic effect was mediated locally rather than systemically.

Iontophoresis and phonophoresis are technologies that are capable of enhancing drug penetration through the skin. Phonophoresis uses ultrasonic waves to transmit molecules of drug through the skin, as opposed to iontophoresis, which uses low level electric current. Both techniques are used to treat inflammatory conditions such as arthritis, plantar fasciitis, tendonitis, bursitis, and carpal tunnel syndrome.Iontophoresis: Many ionic drugs are available including several antivirals, various antibiotics, and other specific drugs. Iontophoresis of ionized drugs provided a 20-60 fold increase in penetration over topical application. Examples of successful applications of iontophoresis include:

Treatment of inflammation/pain of muscles and tendons, including the Achilles tendon

An alternative to steroid injections for therapy of Carpal Tunnel Syndrome

Rreatment for scar and tendon adhesions

Phonophoresis (or sonophoresis) combines ultrasound with topical drug therapy to achieve therapeutic drug concentrations at target sites below the skin. A cream or gel containing medications such as corticosteroids, local anesthetics, electrolytes, or antibiotics is applied to the treatment area and then massaged with a transducer head. The technique has been widely used in sports medicine since the 1960s by podiatrists, orthopedists, and physical therapists.

The method of preparation and quality of ingredients used for solutions or gels for iontophoresis or phonophoresis are critical to the success of the therapy and minimizing side effects.

All formulations are customized per prescription to meet the unique needs of each patient. Please call us to discuss the dosage form, medication, and strength which are most appropriate for your patient.